# The Retinal Dopaminergic Circuit as a Biomarker for Huntington’s and Alzheimer’s Diseases

## TL;DR

This study shows that changes in the retina's dopamine system may serve as an early sign of Huntington’s and Alzheimer’s diseases.

## Contribution

The study identifies retinal dopaminergic dysfunction as a novel early biomarker for Huntington’s and potentially Alzheimer’s diseases.

## Key findings

- HD mice showed early retinal dopamine changes before motor symptoms or brain pathology appeared.
- AD mice showed mild retinal changes at later stages, but human AD may show similar changes earlier.
- Retinal assessments like electroretinography could be non-invasive tools for early diagnosis of neurodegenerative diseases.

## Abstract

Retinal dysfunction is emerging as a potential early marker of neurodegenerative diseases. Within the retina, the dopaminergic circuit, comprising dopaminergic amacrine cells, dopamine synthesis and turnover, and dopamine receptor signalling, is essential for visual processing, particularly colour contrast perception. Disruption of this circuit may underline early retinal alterations observed in Huntington’s disease (HD) and Alzheimer’s disease (AD). In this study, we systematically analysed retinal dopaminergic dysfunction in murine models of HD (genetic origin) and AD (sporadic), across different disease stages. We assessed dopamine levels, turnover, tyrosine hydroxylase expression, D1 and D2 receptor gene expression, and neurotransmitter balance. HD mice showed early and marked alterations: reduced dopamine content, decreased tyrosine hydroxylase, increased turnover, and downregulation of D1 receptor expression—all preceding motor symptoms and detectable brain pathology. In contrast, AD mice showed only mild changes at later stages; however, clinical evidence suggests that similar dysfunction may occur earlier in human AD. These findings position retinal dopaminergic disruption as a potential early biomarker in HD and possibly in AD. While the current study relies on invasive techniques in animal models, it lays the groundwork for non-invasive retinal assessments, such as electroretinography or optical coherence tomography, as promising tools for early diagnosis and disease monitoring in neurodegeneration.